Pascal G. Doornebosch

Transanal endoscopic microsurgery versus total mesorectal excision of T1 rectal adenocarcinomas with curative intention

PURPOSE After total mesorectal excision (TME) for rectal cancer, pathology is standardized with margin status as a predictor for recurrence. This has yet to be implemented after transanal endoscopic microsurgery (TEM) and was investigated prospectively for T1 rectal adenocarcinomas. PATIENTS AND METHODS Eighty patients after TEM were compared to 75 patients after TME. The study protocol included standardized pathology. TEM patients were eligible when excision margins were negative. RESULTS TEM was safer than TME as reflected by operating time, blood loss, hospital stay, morbidity, re-operation rate and stoma formation (all P<0.001). Mortality after TEM was 0% and after TME 4%. At 5 years after TEM and TME, both overall survival (TEM 75% versus TME 77%, P=0.9) and cancer-specific survival (TEM 90% versus TME 87%, P=0.5) were comparable. Local recurrence rate after TEM was 24% and after TME 0% (HR 79.266, 95% CI, 1.208 to 5202, P<0.0001). CONCLUSION For T1 rectal adenocarcinomas TEM is much saver than TME and survival is comparable. After TEM local recurrence rate is substantial, despite negative excision margins.

Treatment of recurrence after transanal endoscopic microsurgery (TEM) for T1 rectal cancer.

PURPOSE: The aim of this study was to evaluate the management and outcome of local recurrences after transanal endoscopic microsurgery for T1 rectal cancer. METHODS: Consecutive patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer at a Dutch referral center (IJsselland Hospital) were registered in a prospective database. Follow-up was according to Dutch guidelines on rectal cancer, with additional rigid rectoscopy and endorectal ultrasound examinations every 3 months for the first 2 years, and every 6 months thereafter. Annual MRI of the lesser pelvis was added during the last 2 years of the study. Patients with local recurrence during follow-up were selected for individual analysis of outcome. RESULTS: Of a total of 88 patients who underwent transanal endoscopic microsurgery for pT1 rectal cancer, 18 patients (20.5%) had a local recurrence. Median time to local recurrence was 10 (range, 4–50) months. Median age at diagnosis of recurrence was 74 (range, 56–84) years. Of the 18 patients, 2 did not undergo further surgery because of concomitant metastatic disease, and 16 underwent salvage surgery, without need for multivisceral resections. No postoperative mortality was observed. In 15 patients (94%), a microscopically negative excision margin was obtained; in 1 patient, the excision margin was microscopically positive. Median follow-up after salvage surgery was 20 (range, 2–112) months. One patient had a local renewal of recurrence, and 7 patients (39%) had distant metastases. At 3 years, overall survival was 31%; cancer-related survival was 58%. CONCLUSIONS: Recurrent disease after transanal endoscopic microsurgery for T1 rectal cancer is a major problem. Although salvage surgery for achieving local control is feasible in most patients, survival is limited, mainly because of distant metastases. Tailoring selection of T1 rectal cancers and exploring possible adjuvant treatment strategies following salvage procedures should be the next steps toward improving survival.

Transanal endoscopic microsurgery for rectal cancer

If curation is intended for rectal cancer, total mesorectal excision with autonomic nerve preservation (TME) is the gold standard. Transanal resection is tempting because of low mortality and morbidity rates. However, inferior tumour control, provoked by the limitations of the technique, resulted in its cautious application and use mainly for palliation. Transanal endoscopic microsurgery (TEM) is a minimal invasive technique for the local resection of rectal tumours. It is a one-port system, introduced transanally. An optical system with a 3D-view, 6-fold magnification and resolution as the human eye, together with the creation of a stabile pneumorectum, and specially designed instruments allow full-thickness excision under excellent view and a proper histological examination. The technique can also be applied for larger and more proximal tumours. Mortality, morbidity as well as incomplete excision rates are minimal. Local recurrence and survival rates seem comparable to TME in early rectal cancer. TEM is the method of choice when local resection of rectal cancer is indicated. Results justify a re-evaluation of the indications for the local excision of rectal cancer with a curative intent.

Quality of life after transanal endoscopic microsurgery and total mesorectal excision in early rectal cancer

Objective  Total mesorectal excision (TME) is the gold standard in rectal cancer, if curation is intended. Transanal endoscopic microsurgery (TEM) is a much safer technique and seems to have comparable survival in early rectal cancer. The impact of both procedures on quality of life has never been compared. In this study we compared quality of life after TEM and TME.

The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery

BackgroundThe CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer.Methods/DesignPatients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol.DiscussionThe CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051)

Transanal Employment of Single Access Ports Is Feasible for Rectal Surgery

Objective:To evaluate the feasibility of transanal single port surgery in 15 consecutive patients. Background:The current method of choice for local resection of rectal tumors is transanal endoscopic microsurgery (TEM), a complex and expensive technique. Single access surgery is easy, relatively cheap, and more broadly applied in laparoscopy. Evidence regarding transanal use of single access ports is scarce. Methods:Consecutive patients with a rectal lesion otherwise eligible for TEM were operated using the Single Site Laparoscopic Access System (SSL) and standard laparoscopic instrumentation. Patient, lesion and procedure characteristics, hospitalization length, and peroperative and postoperative complications were recorded. Results:Fifteen patients were planned for single port transanal surgery. In 2 patients (13.3%), intrarectal retractor expansion failed, and conversion to conventional TEM was necessary. The remaining 13 patients were successfully operated. Rectal lesions (mean diameter 36 mm, standard deviation ±25 mm, mean distance from the dentate line 6 cm [±4.5]) included adenoma in 7 patients, T1 adenocarcinoma in 1, T2 adenocarcinoma in 3, carcinoid in 1, and fibrosis only in 1 (after prior polypectomy). All patients were operated in lithotomy position. Resections were en bloc, full thickness, and had complete margins. Resection specimens measured 65 (±35) × 52 (±24) mm. Twelve rectal defects were sutured. One peroperative pneumoscrotum occurred. Mean operating time was 57 (±39) minutes. One patient presented with postoperative hemorrhage, treated conservatively (postoperative morbidity rate 7.7%). Mean hospitalization lasted 2.5 days (±2.7). Conclusions:Transanal single port surgery via the SSL is feasible and safe and may become a promising alternative to TEM.

Transanal endoscopic microsurgery is feasible for adenomas throughout the entire rectum: A prospective study

INTRODUCTION: Transanal endoscopic microsurgery for rectal adenomas is safe and has low recurrence rates. However, the feasibility of the procedure for all rectal adenomas is unclear. This issue was investigated prospectively. METHODS: From 1996 to 2007, 353 consecutive rectal adenomas were evaluated according to a standard protocol. Transanal endoscopic microsurgery was intended in all rectal adenomas. RESULTS: The median diameter was 3 cm and median distance was 8 cm. The peritoneum was opened peroperatively without any adverse effects in 8.7 percent. The conversion rate was 9.6 percent, with an alternative local procedure performed in 4.2 percent and a transabdominal procedure performed in 5.4 percent. Conversion rate correlated with the distance of the tumor (P = 0.007) and the operating surgeons level of experience (P = 0.004). The median operation time was 45 minutes. Operation time correlated with specimen area, experience, and operating surgeon (all P < 0.001). All rectal adenomas were excised in one piece. Complete margins were observed in 85 percent. Rectal adenomas with incomplete margins were larger (P < 0.001) and were located more proximally (P < 0.001). Morbidity was 7.8 percent and mortality 0.6 percent. The median hospital stay was four days. The median follow-up was 27 months. The recurrence rate at three years was 9.1 percent. The median time from operation to recurrence was 12 (range, 4-54) months. Resection margin status was a predictor of recurrence, with 6.1 percent recurrence in cases of complete margins and 25.2 percent in cases of incomplete margins (P < 0.001). CONCLUSIONS: For nearly all rectal adenomas, transanal endoscopic microsurgery is safe, feasible, and has excellent results.

Is the increasing role of Transanal Endoscopic Microsurgery in curation for T1 rectal cancer justified? A systematic review

Driven by the aim to avoid a permanent colostomy and also the morbidity and mortality of major radical surgery for rectal cancer, the proportion of patients with rectal cancer treated by local excision has increased the last ten years or so. In T1 carcinomas local excision is considered a curative option in selected tumors. However, the scientific base upon which this treatment regimen is built remains controversial. In this systematic review we try to elucidate current literature regarding local excision for T1 rectal carcinomas. Several questions are addressed. First, is there enough evidence to propagate LE as a curative option in selected (T1) rectal carcinomas? Second, if LE is justified, which technique should be the method of choice? Third, can we adequately identify, pre- and postoperatively, tumors suitable for LE? Finally, future perspectives are discussed.

Progression and Tumor Heterogeneity Analysis in Early Rectal Cancer

Purpose: Adequate preoperative staging of large sessile rectal tumors requires identifying adenomas that already contain an invasive focus, specifically those that are growing in or beyond the submucosa. We systematically compared chromosomal instability patterns in adenoma and carcinoma fractions of the same lesion to assess specific steps in rectal tumor progression. Experimental Design: We analyzed 36 formalin-fixed, paraffin-embedded tumors. Both the adenoma and carcinoma fractions were typed with single nucleotide polymorphism arrays and compared with 21 previously described pure adenomas. Eighteen cases were included in an intratumor heterogeneity analysis. Results: Five specific “malignant” events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas. Paired analysis revealed that 31% of the samples had an equal amount of malignant aberrations in their adenoma and carcinoma fractions, whereas 25% had one and 33% had two or more extra malignant events in the carcinoma fraction. Analysis of three core biopsies per patient showed a large degree of intratumor heterogeneity. However, the number of malignant aberrations in the biopsy with the most aberrations per tumor correlated with the corresponding adenoma or carcinoma fraction (r = 0.807; P < 0.001). Conclusion: Five specific chromosomal aberrations, combined with immunohistochemistry for p53 and SMAD4, can predict possible progression of sessile rectal adenomas to early rectal cancer and can, after validation studies, be added to preoperative staging. Preferably, three biopsies should be taken from each tumor to address intratumor heterogeneity.

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

BackgroundRecent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications.The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas.Methods/designMulticenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma ≥ 3 cm, located between 1–15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment.Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures.Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group.DiscussionThe TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas.Trial registration number(trialregister.nl) NTR1422